The project will attempt to elucidate the identity, three-dimensional relationships, and chemical properties of the groups which are responsible for the catalysis of conversion of delta-aminolevulinic acid to porphobilinogen by the enzyme delta-aminolevulinic acid dehydratase from bovine liver. The tools to be used are probes in the form of substrate inhibitors. Work will include inhibition by stereoisomers of substrate analogs and affinity labeling to identify active site residues. The enzyme under study is a suspected locus for the effects of lead poisoning. Experiments are proposed to study the interactions of various divalent metal ions, including the native zinc and paramagnetic manganese as well as lead, with the apoenzyme.